A better understanding of how the neural circuits underlying associative learning and memory change in aging brain and may be related to age- associated learning deficits will be sought. Our strategy will be to study brain system activity in young and aging subjects in parallel with changes in behavior during the acquisition of a well-defined behavioral paradigm and in reference to appropriate control conditions. Functional magnetic resonance imaging (fMRI) will be used in conscious subjects to simultaneously examine conditioning-specific hemodynamic changes during acquisition and consolidation of eyeblink conditioning. The circuitry within the frontal cortex, hippocampus and associated temporal cortex, basal ganglia and cerebellum will be examined. These regions are chosen for emphasis because of their demonstrated involvement in the eyeblink conditioning task in both animals and in humans, and because they are likely to change in important ways during the aging process. The first specific aim is to compare the light conditioned stimulus (CS) and corneal air puff unconditioned stimulus (US) pathways with fMRI at baseline before learning. The second specific aim will be to examine the circuit activated during a 500 msec trace conditioning paradigm which is learned equivalently by young and aging subjects. The third specific aim will be to examine the circuit activated during a 1000 msec trace eyeblink conditioning paradigm in which aging subjects will show a deficit. We hypothesize that this paradigm will more thoroughly activate the frontal cortex and hippocampus/temporal lobe and thus be more likely to detect functional differences due to reduced function in these regions during the aging process. We expect that these experiments will yield significant information regarding the location of changes in hemodynamic activity during associative learning and after aging throughout the frontal cortex-limbic-cerebellar system. The will provide the basis for a noninvasive functional technique to evaluate the effectiveness of potential therapeutic agents for enhancing neural system function during learning and memory in conditions such as normal aging and Alzheimer's Disease. They will also enhance our ability to further understand the neurobiological substrates of associative learning in the human brain.